Metabonomic Approach to Evaluating Pharmacodynamics of Ginkgo biloba Extract on the Perturbed Metabolism in Hamsters with Atherosclerosis by High Fat Diet

Abstract

Aim To investigate the effects of Ginkgo biloba extract (GBE) on the perturbed metabolism of a diet-induced atherosclerosis hamster model. Methods Gas chromatography coupled with time-of-flight mass spectrometry (GC/TOF-MS) spectroscopy was used to profile serum samples of hamsters induced by high fat diet for 0, 3, 6, 12 weeks, and hamsters administered with GBE in the meanwhile. Multivariate analyses were employed to identify treatment-related fingerprint and potential biomarkers regarding the anti-atherosclerosis effect and mechanisms of GBE. Results For the model animals, high fat diet (HFD) resulted in a gradual elevation of serum cholesterol and triglyceride, low-density lipoprotein cholesterol (LDL-C), lesion in aorta arch, and a dynamic trajectory of the metabonomic profile. GBE treatment did not only lead to a marked reduction in total cholesterol and LDL-C levels in hamster serum, but also showed regulatory effects on serum metabolome and restored their scores plot close to normal. Amongst the discriminatory metabolites in serum that characterize atherosclerosis, 8 metabolites restored to normal after treatment with GBE, including succinic acid, glyceric acid, linoleic acid, arachidonic acid, 1-monooleoylglycerol, β-tocopherol, cholest-5-ene, lysine, while 6 metabolites were regulated towards normal, including tyrosine, oleic acid, 2-monooleoylglycerol, γ-tocopherol, α-tocopherol and deoxycholic acid. Conclusion These results indicate that the effect of GBE on the metabolites is involved in lipid metabolism, bile acid synthesis and amino acids turn-over, and is indirect in anti-atherosclerosis effect of GBE. GC/MS-based metabonomics is a potential approach to exploring pharmacological mechanism of GBE effects and to the assessment of pharmacodynamics.